What Research Is Being Done?

Current research focuses on many different aspects of dementia. This research promises to improve the lives of people affected by the dementias and may eventually lead to ways of preventing or curing these disorders.

Causes and prevention

Research on the causes of AD and other dementias includes studies of genetic factors, neurotransmitters, inflammation, factors that influence programmed cell death in the brain, and the roles of tau, beta amyloid, and the associated neurofibrillary tangles and plaques in AD. Some other researchers are trying to determine the possible roles of cholesterol metabolism, oxidative stress (chemical reactions that can damage proteins, DNA, and lipids inside cells), and microglia in the development of AD. Scientists also are investigating the role of aging-related proteins such as the enzyme telomerase.

Since many dementias and other neurodegenerative diseases have been linked to abnormal clumps of proteins in cells, researchers are trying to learn how these clumps develop, how they affect cells, and how the clumping can be prevented.

Some studies are examining whether changes in white matter - nerve fibers lined with myelin - may play a role in the onset of AD. Myelin may erode in AD patients before other changes occur. This may be due to a problem with oligodendrocytes, the cells that produce myelin.

Researchers are searching for additional genes that may contribute to AD, and they have identified a number of gene regions that may be involved. Some researchers suggest that people will eventually be screened for a number of genes that contribute to AD and that they will be able to receive treatments that specifically address their individual genetic risks. However, such individualized screening and treatment is still years away.

Insulin resistance is common in people with AD, but it is not clear whether the insulin resistance contributes to the development of the disease or if it is merely a side effect.

Several studies have found a reduced risk of dementia in people who take cholesterol-lowering drugs called statins. However, it is not yet clear if the apparent effect is due to the drugs or to other factors.

Early studies of estrogen suggested that it might help prevent AD in older women. However, a clinical study of several thousand postmenopausal women aged 65 or older found that combination therapy with estrogen and progestin substantially increased the risk of AD. Estrogen alone also appeared to slightly increase the risk of dementia in this study.

A 2003 study found that people with HIV-associated dementia have different levels of activity for more than 30 different proteins, compared to people who have HIV but no signs of dementia. The study suggests a possible way to screen HIV patients for the first signs of cognitive impairment, and it may lead to ways of intervening to prevent this form of dementia.

Diagnosis

Improving early diagnosis of AD and other types of dementia is important not only for patients and families, but also for researchers who seek to better understand the causes of dementing diseases and find ways to reverse or halt them at early stages. Improved diagnosis can also reduce the risk that people will receive inappropriate treatments.

Some researchers are investigating whether three-dimensional computer models of PET and MRI images can identify brain changes typical of early AD, before any symptoms appear. This research may lead to ways of preventing the symptoms of the disease.

One study found that levels of beta amyloid and tau in spinal fluid can be used to diagnose AD with a sensitivity of 92 percent. If other studies confirm the validity of this test, it may allow doctors to identify people who are beginning to develop the disorder before they start to show symptoms. This would allow treatment at very early stages of the disorder, and may help in testing new treatments to prevent or delay symptoms of the disease. Other researchers have identified factors in the skin and blood of AD patients that are different from those in healthy people. They are trying to determine if these factors can be used to diagnose the disease.

Treatment

Researchers are continually working to develop new drugs for AD and other types of dementia. Many researchers believe a vaccine that reduces the number of amyloid plaques in the brain might ultimately prove to be the most effective treatment for AD. In 2001, researchers began one clinical trial of a vaccine called AN-1792. The study was halted after a number of people developed inflammation of the brain and spinal cord. Despite these problems, one patient appeared to have reduced numbers of amyloid plaques in the brain. Other patients showed little or no cognitive decline during the course of the study, suggesting that the vaccine may slow or halt the disease. Researchers are now trying to find safer and more effective vaccines for AD.

Researchers are also investigating possible methods of gene therapy for AD. In one case, researchers used cells genetically engineered to produce nerve growth factor and transplanted them into monkeys' forebrains. The transplanted cells boosted the amount of nerve growth factors in the brain and seemed to prevent degeneration of acetylcholine-producing neurons in the animals. This suggests that gene therapy might help to reduce or delay symptoms of the disease. Researchers are now testing a similar therapy in a small number of patients. Other researchers have experimented with gene therapy that adds a gene called neprilysin in a mouse model that produces human beta amyloid. They found that increasing the level of neprilysin greatly reduced the amount of beta amyloid in the mice and halted the amyloid-related brain degeneration. They are now trying to determine whether neprilysin gene therapy can improve cognition in mice.

A clinical trial called the Vitamins to Slow Alzheimer's Disease (VITAL) study is testing whether high doses of three common B vitamins - folic acid, B12, and B6 - can reduce homocysteine levels and slow the rate of cognitive decline in AD.

Since many studies have found evidence of brain inflammation in AD, some researchers have proposed that drugs that control inflammation, such as NSAIDs, might prevent the disease or slow its progression. Studies in mice have suggested that these drugs can limit production of amyloid plaques in the brain. Early studies of these drugs in humans have shown promising results. However, a large NIH-funded clinical trial of two NSAIDS (naproxen and celecoxib) to prevent AD was stopped in late 2004 because of an increase in stroke and heart attack in people taking naproxen, and an unrelated study that linked celecoxib to an increased risk of heart attack.

Some studies have suggested that two drugs, pentoxifylline and propentofylline, may be useful in treating vascular dementia. Pentoxifylline improves blood flow, while propentofylline appears to interfere with some of the processes that cause cell death in the brain.

One study is testing the safety and effectiveness of donepezil (Aricept) for treating mild dementia in patients with Parkinson's dementia, while another is investigating whether skin patches with the drug selegiline can improve mental function in patients with cognitive problems related to HIV.